Drug abuse has forced our country to spend millions of dollars in the clinical treatment and prevention of addiction. The scientific community has also invested extensively in understanding the causes of addiction. Our advances in understanding the basic science of this disease are at a point requiring an evaluation of how drugs of abuse mediate the psychological component of addiction. The CART (Cocaine- and Amphetamine- Regulated Transcript) gene encodes a novel family of neurotransmitters implicated in mediating the effects of stimulant drugs of abuse. Research has also demonstrated a physiological role for CART peptides in the control of feeding, resembling the inhibitory effects of cocaine on food intake. It is proposed that CART peptide receptors are present in the brain. This experimental research plan has been designed to identify these CART peptide receptors. A series of CART peptides will be generated and tested for biological activity. The significance of this first aim will be to characterize CART peptides for agonist or antagonistic activity so they can be of use in future studies. In addition, we will characterize the phenotype of the CART peptide responsive pituitary cells as this assay was used to determine peptide biological activity. These results will provide a means from which receptor identification can begin. The second aim is to determine CART peptide binding sites and their distribution in the brain. This information will facilitate the cloning of the CART peptide receptors in the future. The results of these experiments will lead to a better understanding of the biology of reward and reinforcement. Ultimately, these results may lead to the development of pharmacotherapeutic agents to treat substance abuse and addictive behaviors.